Salicylic acid, FEMA 3985, SALICYLIC ACID, Medical Salicylic Acid, 69-72-7 

Salicylic acid, FEMA 3985, SALICYLIC ACID, Medical Salicylic Acid, 69-72-7 

CAS: 69-72-7

Molecular Formula: C7H6O3

Names and Identifiers

Physico-chemical Properties

Risk and Safety

Upstream Downstream Industry

Introduction

salicylic acid, also known as the acid, for white crystalline powder, odorless, the taste of the first slightly bitter and then turn into Xin. Found in nature in willow bark, white-bead leaves, and sweet birch. Chemical formula C6H4(OH)(COOH), melting point 157-159 ℃, in the light gradually color change. The relative density was 1.44. The boiling point is about 211 °c/2.67kPa. 76 degrees C sublimation. Under atmospheric pressure, it is rapidly decomposed into phenol and carbon dioxide by heating. Soluble in ethanol, ether, chloroform, benzene, acetone, turpentine, not soluble in water. 1g of salicylic acid can be dissolved in 460ml of water, 15ml of boiling water, 2.7ml of ethanol, 3ml of acetone, 3ml of ether, 42ml of chloroform, 135ml of benzene, 52ml of turpentine, about 60ml of glycerol and 80ml of petroleum ether, respectively. Adding sodium phosphate, borax etc. can increase the solubility of salicylic acid in water. The pH of the salicylic acid aqueous solution was 2.4. Salicylic acid with ferric chloride in water produces a special purple color.

Important raw materials for organic synthesis

• salicylic acid is an important organic synthetic raw material, widely used in medicine, pesticide, rubber, dye, food and perfume industry. In the pharmaceutical industry, salicylic acid for the production of the main drugs are sodium salicylate, oil of wintergreen (methyl salicylate), aspirin (acetylsalicylic acid), salicylic acid amine, phenyl salicylate and so on. In the dye industry for the production of mordant yellow, direct yellow 3GN, direct yellow GR, direct Brown 3GN, acid mordant Brown G, acid mordant yellow GG, acid yellow and other dyes. In the production of pesticides, salicylic acid is used for the synthesis of isopropyl salicylate, an intermediate of The organophosphorus insecticides isocarbophos and methyliisophos, and 4-hydroxycoumarin, an intermediate of the rodenticide and rodenticide. In the rubber industry as scorch retarder and the production of ultraviolet absorber and foaming agent. Spices raw materials, preparation of methyl salicylate, Ethyl salicylate, etc.; Food preservatives, the use of its sodium salt, now some countries have been banned; Methyl salicylate can be used as a mouth cleaner, such as toothpaste spices.
• salicylic acid has the ability to kill bacteria, 2.5% alcohol solution (called salicylic acid) commonly used as the treatment of tinea Manus and tinea pedis external medicine, can also be formulated into ointment use. Sodium salicylate may be used as a food preservative or preservative, and may also be used in the formulation of toothpastes, mouthwashes, and the like. Salicylic acid has antipyretic and analgesic effects, can treat rheumatism. Its various esters are useful as pharmaceuticals and fragrances. Methyl salicylate has a pleasant fragrance of wintergreen and is used in the preparation of perfumes and soap essences. Methyl salicylate applied to the skin, can penetrate into the muscle and release salicylic acid and local pain, and thus can also be used for the treatment of pain, contusion, sprain and other external drugs. Isoamyl salicylate has a orchid-like aroma, and benzyl salicylate has a faint aroma, which can be used to prepare perfume or soap essence. Phenyl salicylate, commonly known as Salo, is hydrolyzed to phenol and salicylic acid in the intestine and is an effective intestinal preservative. Another drug related to salicylic acid is p-aminosalicylic acid (PAS for short, see "p-aminosalicylic acid"), whose sodium and calcium salts are used as anti-tuberculosis drugs for Acute exudative tuberculosis and mucosal tuberculosis, is a weak antibacterial agent, the role of only 2% of streptomycin, often combined with streptomycin, isoniazid, in order to enhance the efficacy. Acetylating it can make aspirin.

Nature

White needle-like crystals or monoclinic prisms with spicy flavor. Flammable. Low toxicity. Stable in air, but gradually change color in light. Melting point 159 °c. The relative density was 1. 443. Boiling Point 211 °c. Sublimation at 76 °c. Slightly soluble in water, soluble in acetone, turpentine, ethanol, ether, benzene and chloroform. Its aqueous solution is acidic.

Preparation Method

phenol reacts with sodium hydroxide to generate sodium phenolate. After distillation and dehydration, sodium salicylate is obtained by carboxylation with carbon dioxide, and then acidified with sulfuric acid to obtain crude product. The crude product is refined by sublimation to obtain the finished product.

Standard

This product is 2-Hydroxybenzoic acid. The content of C7H603 shall not be less than 99.5%.

Trait

• This product is white fine needle-like crystal or white crystalline powder; Odorless or almost odorless; Acidic reaction in aqueous solution.
• This product is soluble in ethanol or ether, soluble in boiling water, slightly soluble in three gas methane, slightly soluble in water.

melting point

The melting point of this product (General 0612) is 158~161°C.

Chemical properties

• salicylic acid, also known as sulinic acid, is more acidic than benzoic acid, darkened in the sun, iron ions into a purple-red chelate, and ferric chloride reaction is purple, unstable to heat, it is easily decarboxylated to phenol by heating to 200 °c. In nature, salicylic acid exists in the form of methyl ester in birch bark oil, and the content can reach 96%. Also present in cinnamon oil, violet oil, wintergreen oil. Free salicylic acid is only present in small amounts in plants.
• salicylic acid has a dual nature of phenol and carboxylic acid. Sublimation when heated, rapid heating, the decomposition of phenol and carbon dioxide. Reaction with sodium hydroxide, hydroxyl and carboxyl groups are neutralized, the formation of double salt; But with sodium carbonate, only the carboxyl group is neutralized to form a single salt. When reacting with an alcohol or a phenol, the corresponding salicylate can be formed; When acting with a carboxylic acid or an acid anhydride, the corresponding carboxylate can be formed. This product is toxic, stimulate the skin, mucous membranes, can react with the body tissue protein, it is corrosive, on the other hand, it can be sterilized. Rat oral LD501100 ~ 1600mg/kg. Storage is stable, but the powder can produce an explosion when mixed with air.
• It is industrially prepared by reacting phenol sodium salt with carbon dioxide under heating and pressure (Kolbe-Schmitt reaction). First, phenol is neutralized with sodium hydroxide to form phenol sodium salt, then, carbon dioxide is absorbed at 105 Pa ° C. Under 4-7 × 125 (4-7 atmospheres) to form phenyl sulfonate, which is rearranged to form sodium salicylate and acidified to form salicylic acid.

Use

used as a raw material for medicines (such as aspirin), food preservatives and spices. In the dye industry for the manufacture of medium pure yellow, direct Brown 3GN, Acid chrome yellow. It can also be used as rubber vulcanization retardant and Disinfection preservative.

Differential diagnosis

1. take the aqueous solution of this product and add 1 drop of three-gas Iron Test Solution to show the color of Corydalis.
2. The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 57).

Effect

salicylic acid is widely used, eczema, psoriasis, acne, dandruff may be used salicylic acid. Salicylic acid concentration in 3% ~ 6% can be used to exfoliate, more than 6% is destructive to the tissue. Below 40% concentration is suitable for the treatment of corns, thick cocoon, virus warts. Salicylic acid can also be added in the treatment of acne and anti dandruff drugs. Now a lot of well-known cosmetics add salicylic acid ingredients: 1993 CLINIQUE first launched containing 1% salicylic acid ingredients of the soft renewal of the water cream, immediately become one of the most successful CLINIQUE products; in SK-II, 1.5%, BHA was added to the original Pitera formula, and the effect of salicylic acid in treating pores and cutin was compared with the shell egg, which caused the market boom; open-shelf pathway of the popular product of the skin essence cream also contains 1.5% BHA ingredients. However, due to the high concentration of salicylic acid has a certain degree of harm, cosmetics containing salicylic acid concentration is generally limited between 0.2% ~ 1.5%, containing salicylic acid cosmetics must be added warning signs to determine the safety of long-term use, and not for children under 3 years of age.

Safety

• This product stimulates the skin and mucous membrane, and can react with the protein in the body tissue, so it has a corrosive effect. Can make the corneal proliferation after peeling. Its toxicity is weaker than that of phenol, but it can cause Vomit, Diarrhea, Head Pain, sweating, rash, respiratory frequency, acidosis and excitement. Severe when Dyspnea, collapse, eventually heart paralysis and death. Due to the excretion of salicylic acid from the kidneys, often cause acute nephritis. Rabbit oral LDl. 3g/kg. Operators should wear labor protection equipment.
• The packing is packed in plastic-lined plastic bags, jacket hemp bags or polypropylene woven bags or fiberboard barrels. Store in a cool, dry, ventilated warehouse, and explosive, oxidant Isolation. Protected from light.

Exam

Related substances

take 0.5g of this product, precise weighing, put it in a 100ml measuring flask, add the mobile phase to dissolve and dilute to the scale, as a test solution; Take lml for precision measurement, in a 50ml measuring flask, dilute to scale with mobile phase, shake well, and then take 1 ml with precision. In a 10ml measuring flask, dilute to scale with mobile phase, shake well, and use as a control solution. Take appropriate amount of 4-hydroxybenzoic acid, 4-hydroxyisophthalic acid and phenol reference substance, add mobile phase to dissolve and dilute to make about 5ug of 4-hydroxybenzoic acid, A mixed solution of 2.5ug of 4-hydroxyisophthalic acid and 1ug of phenol was used as a reference solution. According to the determination method of high performance liquid chromatography (General rule 0512), silica gel bonded with eighteen alkyl silane was used as the filler; Methanol-water-glacial acetic acid (60:40:1) was used as the mobile phase; The detection wavelength was 270nm. 20 u1 of each of the reference solution, test solution and control solution were accurately measured and injected into the human liquid chromatograph respectively, and the chromatogram was recorded to 2 times of the retention time of the main component peak. If there is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of the reference solution, the peak area shall be calculated by the external standard method, and the 4-hydroxybenzoic acid shall not exceed 0.1%, and the 4-hydroxyisophthalic acid shall not exceed 0.05%, phenol shall not exceed 0.02%; Other single impurity peak area shall not be greater than 0.25 times (0.05%) of the main peak area of the control solution; The sum of each impurity peak area shall not be greater than the main peak area of the control solution (0.2%).

ignition residue

not more than 0.1% (General rule 0841).

Heavy metals

take l.Og of this product, add 23ml of ethanol to dissolve, add acetate buffer (pH3.5)2ml, check according to law (General rule 0821 first law), containing heavy metals not more than 10 parts per million.

Compared with the cosmetic effect of acid

Open Data Unverified Data

salicylic acid (BHA) is extracted from willow bark, Ilex leaves, also known as plant acid; Fruit acid (AHA) is extracted from sugar cane; Acid is extracted from two different raw materials. Both can control oil, exfoliation, remove acne, narrow pores, light. The concentration of more than 50% of the acid can only be operated by a dermatologist, and salicylic acid, regardless of the concentration of the skin, are classified as medical treatment, it is worth noting that a small number of people are not suitable for the use of any concentration of salicylic acid, so the general beauty room can not be implemented, in the beauty room to implement the concentration of 40% or less of the fruit acid is allowed by law, in contrast, fruit acid is much safer than salicylic acid. As for the effect, salicylic acid is only locked in the superficial stratum corneum, but only plays a role of simple treatment and blocking, changing the skin is only temporary, and the acid enters the dermis to fundamentally change the skin, it can be cured, as for the formation of dermal damage, the role of salicylic acid is unable to do so, so salicylic acid can not be called "salicylic acid skin change", can only be called "salicylic acid treatment". The safety and effect of salicylic acid and acid are different, because the acid is not toxic, can be used from low to high (8% -15%-20%-30%-40%), slow adaptation is not burn the skin, disfigurement and any side effects. And salicylic acid is toxic, too high concentration is not suitable for use on the face, there is a certain concentration limit, the concentration of 3%-6% of salicylic acid can be used to exfoliate, more than 6% is corrosive to the skin, and a high concentration of 40% salicylic acid has strong keratolytic properties.

Content determination

take about 0.3g of this product, weigh it precisely, add 25ml of neutral dilute ethanol (neutral to phenolphthalein indicator solution), add 3 drops of phenol indicator solution, with sodium hydroxide titration solution (0.lmol/L) titration. Each l of sodium hydroxide titration solution (0.1 mol/L) corresponds to 13.81mg of C7H603.

 Precautions

• for general skin care, a small number of users, should not have systemic side effects. However, for a large range (greater than 30% of the total body area) or long-term use of salicylic acid, special attention should be paid to the toxic effect of salicylic acid. Including tinnitus, dizziness, burnout, Nausea and electrolyte imbalance, should immediately stop using.
• salicylic acid can cause contact dermatitis. After large-area use and absorption, salicylic acid can appear systemic poisoning symptoms, such as dizziness, confusion, shortness of breath, persistent tinnitus, severe or persistent Head Pain, tingling. With diabetes, peripheral vascular disease, or infants, the use of salicylic acid 25%-60% cream or ointment, salicylic acid 15%-50% cream, salicylic acid 17% gel, salicylic acid 13.6%-26% solution should be carefully considered, it may cause inflammation or ulcers, or even death; For dermatitis or skin infections, the use of salicylic acid 25%-60% cream or ointment, salicylic acid 40%-50% cream, also need to pay attention.

Category

Disinfection antiseptic.

Maximum allowable amount of food additive, maximum allowable residue

The Chinese name of the additive is allowed to use the Chinese name of the food additive function maximum allowable usage (g/kg) maximum allowable residue (g/kg)
2-hydroxy benzoic acid food food spices for the preparation of flavor ingredients of each flavor should not exceed GB2760

of the maximum allowable amount and the maximum allowable residue

Storage

sealed storage.

 Production method

Open Data Unverified Data

• phenol reacts with sodium hydroxide to generate sodium phenolate. After distillation and dehydration, sodium salicylate is obtained by carboxylation with carbon dioxide, and then acidified with sulfuric acid to obtain a crude product. The crude product is refined by sublimation to obtain the finished product. Raw material consumption quota: phenol (98%)704kg/t, caustic soda (95%)417kg/t, sulfuric acid (95%)500kg/t, carbon dioxide (99%)467kg/t.
• the preparation method is obtained by carboxylation of phenol sodium salt and carbon dioxide followed by acidification.
• the phenol sodium salt solution is made from phenol and liquid caustic soda, dried under vacuum, and then the dried carbon dioxide is slowly introduced at 100 ℃. When the pressure reaches 0.7 ~ 0.8MPa, the carbon dioxide is stopped, the temperature was increased to 140-180 °c. After the completion of the reaction, add water, sodium salicylate solution After decolorization, filtration, and sulfuric acid acidification, namely precipitation of salicylic acid, after filtration, washing, drying to obtain the finished product.

Salicylic acid ointment

This product contains salicylic acid (C7H603) should be labeled the amount of 90.0% ~ 110.0%.

trait

This product is yellow soft sound.

identification

1. take about 2g of this product, add 10ml of water, slightly warm, shake, cool, separate the aqueous solution, and add 1 drop of ferric chloride test solution to show Corydalis color.
2. in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.

examination

should be in accordance with the relevant provisions under soft-ware (General rule 0109).

Content determination

• measured by high performance liquid chromatography (General 0512).
• chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler; Methanol-water-glacial acetic acid (50:50:1) as mobile phase; The detection wavelength was 304nm. The number of theoretical plates should not be less than 2000 calculated according to the peak of salicylic acid.
• determination method: take an appropriate amount of this product (about 10mg of salicylic acid), weigh it accurately, put it in a beaker, add 10ml of chloroform, dissolve it by ultrasound, and transfer it quantitatively to a 200ml measuring flask, add an appropriate amount of anhydrous ethanol, ultrasonic to dissolve salicylic acid and dilute to the scale, shake filter, take the filtrate as the test solution, take the 20ul injection liquid chromatograph, record the chromatogram; another appropriate amount of salicylic acid reference substance, precision weighing, plus anhydrous ethanol dissolution and quantitative dilution to make a solution containing about 50ug per lm, the same method for determination. According to the external standard method to calculate the peak area, that is.

Category :Disinfection antiseptic (topical antifungal).

Specification :(1)2% (2)5%

Storage : sealed, stored below 301.

Toxicology

Salicylic acid and its salts poisoning, mostly swallowing a lot, or in the course of treatment caused by excessive doses and frequent administration. Salicylic acid and salts can also be absorbed through the skin and cause poisoning, especially methyl salicylate. Its toxicological effects are:

1. Central nervous system: the effect of this class of drugs on the central nervous system begins with excitation (increased breathing, fear, dysphoria, tremor, convulsions, etc.), edema may even occur.
2. electrolyte and acid balance due to increased breathing, hyperventilation, can cause respiratory alkalosis, after the discharge of the base and the metabolism caused by the salicylic acid salt is changed (due to the inhibition of amino transferase and dehydrogenase by salicylate, inhibition of the metabolism of acetyl-CoA via the tricarboxylic acid cycle results in an increase in ketone bodies). Can cause Metabolic Acidosis.
3. the digestive system has a direct stimulating effect on the digestive tract. Especially with salicylic acid.
4. the toxic dose of cardiovascular system can directly act on the vascular smooth muscle, so that the peripheral vascular tension is reduced, and the work can make the central vascular obstruction, thereby causing circulatory failure.
5. li inhibits the production of prothrombin by the liver and reduces thrombin, thereby causing bleeding.
6. the content of glycogen in the liver, muscle and heart muscle is reduced, the liver and neutral fat are thickened, and the content of vitamin C and cholesterol in the adrenal gland is reduced.
7. li has a stimulating effect on the kidney.

clinical manifestations

poisoning can show Nausea, Vomit, Head Pain, hearing impairment, profuse sweating, flushing, thirst, pale skin, cyanosis, mucosal bleeding, heartburn, liver enlargement, jaundice, rapid pulse, rapid and deep breathing. In addition, water, electrolyte imbalance and poisoning can occur. Sometimes low blood sugar or temporary increase in blood sugar and urine can occur irritability, confusion, convulsions, Coma, Shock and Respiratory Insufficiency.
1. Diagnosis can be made according to the history of drug overdose and the clinical signs of central nervous system and metabolic changes as the main manifestations.
Treatment:

• the patient was given warm water gastric lavage and catharsis.
• Acceleration of excretion: the rate of excretion of salicylates from urine depends on the pH value of urine. When the pH value is 7.5, the excretion of free salicylates is 20-30 times higher than that at pH 6. In order to achieve the purpose of alkalizing urine, can be combined with the application of acetoxazole sulfonic acid and sodium bicarbonate. Acetoxazole iodoamine is a carbonic anhydrase inhibitor that alkalinizes urine by preventing the reabsorption of bicarbonate and is given at a dose of 5mg per kilogram of body weight for a duration of 4 hours. It is difficult to urinate when there is Metabolic Acidosis, and excessive correction may cause metabolic alkalosis, water species, etc., must be noted.
• symptomatic treatment, timely correction of water, electrolyte and acid-base imbalance; Control of convulsions; Prevention of Shock and cerebral edema; Prothrombin time extension and correction of bleeding, large amounts of vitamin K1 can be given intravenously, vitamin K can also be given intramuscularly, and other hemostatic agents can be given; Respiratory inhibitors are contraindicated when breathing is enhanced.
• artificial dialysis therapy can be considered if conditions permit. When peritoneal dialysis is used, it is advisable to add a proper amount of albumin to the dialysate, otherwise, salicylate cannot precipitate rapidly because salicylate has a tendency to bind to serum proteins.

Reference Information